The two Americans, who have not been named, were the only crew aboard the OH-58 Kiowa helicopter, according to a Defense Department official.
The cause of the crash is under investigation and officials have not ruled out that the chopper was shot down.
"Sometimes these things take weeks to determine the actual cause," Maj. Adam Wojack of the International Security Assistance Force said.
The incident happened in Logar Province, an area patrolled mostly by U.S. forces.
The Taliban quickly claimed responsibility, saying one of their fighters shot the aircraft down. Afghan sources in Logar say a heavy firefight broke out after the helicopter crashed.
A NATO helicopter crashed near Kandahar less than a week ago, killing two Australian troops. Another NATO helicopter crashed Aug. 26, described by ISAF as a "hard landing."
No one on board was killed, according to the ISAF.
The Taliban claimed responsibility for both incidents, saying their fighters shot down the aircraft.
ABC News' Luis Martinez contributed to this report.